Long noncoding RNA POU6F2-AS1 regulates lung cancer aggressiveness through sponging miR-34c-5p to modulate KCNJ4 expression

Abstract

It has been extensively reported that long noncoding RNAs (lncRNAs) were closely associated with multiple malignancies. The aim of our study was to investigate the effects and mechanism of lncRNA POU6F2-AS1 in lung adenocarcinoma (LADC).The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) datasets provided us the information of LADC clinical samples. High-regulation of POU6F2-AS1 was presented in LADC tissues compared with adjacent normal tissues, which was correlated with poor outcome of LADC patients. Functional experiments in Calu-3 and NCI-H460 cells showed that POU6F2-AS1 significantly promoted LADC cell proliferation, colony formation, invasion and migration. Moreover, through online prediction, luciferase reporter assay and Pearson's correlation analysis, we found that POU6F2-AS1 may act as a competing endogenous RNA (ceRNA) of miR-34c-5p and facilitated the expression of potassium voltage-gated channel subfamily J member 4 (KCNJ4). The promoting effect of cell aggressiveness induced by POU6F2-AS1 was enhanced by KCNJ4, whilst was abrogated due to the overexpression of miR-34c-5p. Collectively, POU6F2-AS1 might function as a ceRNA through sponging miR-34c-5p to high-regulate KCNJ4 in LADC, which indicates that POU6F2-AS1 might be a promising therapeutic target with significant prognostic value for LADC treatment.

Potassium channels: Novel targets for tumor diagnosis and chemoresistance

“…Kir2.1(KCNJ2) is associated with the development of papillary thyroid carcinoma(PTC), and interference with KCNJ2 inhibits cell proliferation, invasion, migration, and EMT processes ( 38 ). The researchers found that the lncRNA POU6F2-AS1 may act as a competitive endogenous RNA(ceRNA) for miR-34c-5p and promote the expression of Kir2.3(KCNJ4) and enhance the invasiveness of LC cells ( 39 ). Kir6.2(KCNJ11) and Sulfonylurea Receptor(ABCC9) gene expression is downregulated in OC compared to healthy tissues, and expression of Kir6.2 correlates with OC prognosis ( 40 ).…”

“…Kir2.1 is highly expressed in GC and is positively correlated with depth of tumor invasion, metastatic status, and poor overall patient survival, and is a potential prognostic marker and therapeutic target ( 64 ). Kir2.3 overexpression is strongly associated with poor prognosis in patients with LUAD ( 39 ). In OC, minoxidil prevents tumor growth in OC xenograft models by stimulating Kir6.2/SUR2 channels to produce mitochondrial destruction and extensive DNA damage, altering the metabolic and oxidative status of cancer cells ( 40 ).…”

Current advancements and future perspectives of long noncoding RNAs in lipid metabolism and signaling

“…Another Kir2 channel, KCNJ4 (Kir2.3), is also modulated by lncRNA. In human lung adenocarcinoma Calu-3 and NCI-H460 cell lines, lncRNA POU6F2-AS1 can sponge miR-34c-5p and facilitate KCNJ4 expression, promoting the development of lung adenocarcinoma cells [179] .…”